Centralized exhaust system simulation and parameter optimization.

With the increase in high-rise buildings in cities, public flue exhaust systems have a direct impact on residential air quality and the living environment. Although existing studies have analyzed the problems in public flue exhaust systems through computational fluid dynamics (CFD) numerical simulations and experimental tests, these studies often lack an in-depth exploration of the specific impacts of individual components in the system. To solve this problem, this study not only thoroughly analyzes the key components in the public flue system, such as branch pipes, check valves, and tee pipes, but also develops a parametric public flue simulation system software based on C# and verifies the accuracy of the simulation through experiments. The study first determines the key parameters affecting the comprehensive resistance coefficient of the branch pipe, check valve, tee pipe, and other components through CFD simulation and experimental testing. Subsequently, a visualization program is developed using the C# language, which can quickly simulate and visualize the flow changes in the flue according to different building parameters such as the number of floors, height of floors, and size of the flue. The results confirm that the program can efficiently predict the flow distribution under different design options, providing a practical tool for the optimal design and performance evaluation of public flues, which is important for improving the air quality of the living environment.

Application and research progress of single cell sequencing technology in leukemia.

Leukemia is a malignant tumor with high heterogeneity and a complex evolutionary process. It is difficult to resolve the heterogeneity and clonal evolution of leukemia cells by applying traditional bulk sequencing techniques, thus preventing a deep understanding of the mechanisms of leukemia development and the identification of potential therapeutic targets. However, with the development and application of single-cell sequencing technology, it is now possible to investigate the gene expression profile, mutations, and epigenetic features of leukemia at the single-cell level, thus providing a new perspective for leukemia research. In this article, we review the recent applications and advances of single-cell sequencing technology in leukemia research, discuss its potential for enhancing our understanding of the mechanisms of leukemia development, discovering therapeutic targets and personalized treatment, and provide reference guidelines for the significance of this technology in clinical research.

Effect of dietary fibre on cognitive function and mental health in children and adolescents: a systematic review and meta-analysis.

Objective: The purpose of this study is to investigate the impact of dietary fibre on the mental health and cognitive function of children and adolescents. Methods: All interventional and observational studies that contained information on the relevant population (children and adolescents), intervention/exposures (high dietary fibre consumption) and outcomes (mental and cognitive parameters) were eligible. Eight electronic databases (Embase, Medline, Pubmed, Web of Science, Scopus, PsycINFO, Cochrane Library and ClinicalTrials.gov) were searched up to December 11, 2023. Results: A total of 15 studies (n = 4628) met inclusion criteria, consisting of 9 intervention trials and 6 observational studies. According to observational studies, higher dietary fibre consumption was associated with a 49% reduction in the odds of depression compared to lower intake (P < 0.0001; OR = 0.51; 95% CI: 0.38, 0.69; I2 = 0%). Furthermore, no significant correlations were found between dietary fibre consumption and intelligence or anxiety. Among intervention studies, no significant difference was observed between fibre supplementation and placebo in terms of anxiety (standardized mean difference (SMD): -0.23; 95% CI: -0.72, 0.27), stress (SMD: 0.03; 95% CI: -0.21, 0.28), memory (SMD: 0.46; 95% CI: -0.79, 1.71), or attention (SMD: -2.72; 95% CI: -6.30, 0.86). Conclusion: Evidence from observation studies demonstrated that higher dietary fibre consumption is associated with a decreased odds of depression symptoms, both in childhood and adolescence. However, the causal relationship between dietary fibre intake and mental and cognitive function in children and adolescents still requires further clarification through high-quality intervention studies in the future.

Dietary fiber for the prevention of childhood obesity: a focus on the involvement of the gut microbiota.

Given the worldwide epidemic of overweight and obesity among children, evidence-based dietary recommendations are fundamentally important for obesity prevention. Although the significance of the human gut microbiome in shaping the physiological effects of diet and obesity has been widely recognized, nutritional therapeutics for the mitigation of pediatric obesity globally are only just starting to leverage advancements in the nutritional microbiology field. In this review, we extracted data from PubMed, EMBASE, Scopus, Web of Science, Google Scholar, CNKI, Cochrane Library and Wiley online library that focuses on the characterization of gut microbiota (including bacteria, fungi, viruses, and archaea) in children with obesity. We further review host-microbe interactions as mechanisms mediating the physiological effects of dietary fibers and how fibers alter the gut microbiota in children with obesity. Contemporary nutritional recommendations for the prevention of pediatric obesity are also discussed from a gut microbiological perspective. Finally, we propose an experimental framework for integrating gut microbiota into nutritional interventions for children with obesity and provide recommendations for the design of future studies on precision nutrition for pediatric obesity.

Carfilzomib activates ER stress and JNK/p38 MAPK signaling to promote apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers in the world, which is frequently diagnosed at a late stage. HCC patients have a poor prognosis due to the lack of an efficacious therapeutic strategy. Approved drug repurposing is a way for accelerating drug discovery and can significantly reduce the cost of drug development. Carfilzomib (CFZ) is a second-generation proteasome inhibitor, which is highly efficacious against multiple myeloma and has been reported to possess potential antitumor activities against multiple cancers. However, the underlying mechanism of CFZ on HCC is still unclear. Here, we show that CFZ inhibits the proliferation of HCC cells through cell cycle arrest at the G2/M phase and suppresses the migration and invasion of HCC cells by inhibiting epithelial-mesenchymal transition. We also find that CFZ promotes reactive oxygen species production to induce endoplasmic reticulum (ER) stress and activate JNK/p38 MAPK signaling in HCC cells, thus inducing cell death in HCC cells. Moreover, CFZ significantly inhibits HCC cell growth in a xenograft mouse model. Collectively, our study elucidates that CFZ impairs mitochondrial function and activates ER stress and JNK/p38 MAPK signaling, thus inhibiting HCC cell and tumor growth. This indicates that CFZ has the potential as a therapeutic drug for HCC.

Uncovering lupus nephritis-specific genes and the potential of TNFRSF17-targeted immunotherapy: a high-throughput sequencing study.

Introduction: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE). This study aimed to identify LN specific-genes and potential therapeutic targets. Methods: We performed high-throughput transcriptome sequencing on peripheral blood mononuclear cells (PBMCs) from LN patients. Healthy individuals and SLE patients without LN were used as controls. To validate the sequencing results, qRT-PCR was performed for 5 upregulated and 5 downregulated genes. Furthermore, the effect of the TNFRSF17-targeting drug IBI379 on patient plasma cells and B cells was evaluated by flow cytometry. Results: Our analysis identified 1493 and 205 differential genes in the LN group compared to the control and SLE without LN groups respectively, with 70 genes common to both sets, marking them as LN-specific. These LN-specific genes were significantly enriched in the 'regulation of biological quality' GO term and the cell cycle pathway. Notably, several genes including TNFRSF17 were significantly overexpressed in the kidneys of both LN patients and NZB/W mice. TNFRSF17 levels correlated positively with urinary protein levels, and negatively with complement C3 and C4 levels in LN patients. The TNFRSF17-targeting drug IBI379 effectively induced apoptosis in patient plasma cells without significantly affecting B cells. Discussion: Our findings suggest that TNFRSF17 could serve as a potential therapeutic target for LN. Moreover, IBI379 is presented as a promising treatment option for LN.

Myricetin Induces Ferroptosis and Inhibits Gastric Cancer Progression by Targeting NOX4.

Ferroptosis holds great potential as a therapeutic approach for gastric cancer (GC), a prevalent and deadly malignant tumor associated with high rates of incidence and mortality. Myricetin, well-known for its multifaceted biomedical attributes, particularly its anticancer properties, has yet to be thoroughly investigated regarding its involvement in ferroptosis. The aim of this research was to elucidate the impact of myricetin on ferroptosis in GC progression. The present study observed that myricetin could trigger ferroptosis in GC cells by enhancing malondialdehyde production and Fe2+ accumulation while suppressing glutathione levels. Mechanistically, myricetin directly interacted with NADPH oxidase 4 (NOX4), influencing its stability by inhibiting its ubiquitin degradation. Moreover, myricetin regulated the inhibition of ferroptosis induced by Helicobacter pylori cytotoxin-associated gene A (CagA) through the NOX4/NRF2/GPX4 pathway. In vivo experiments demonstrated that myricetin treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice. It was accompanied by increased NOX4 expression in tumor tissue and suppression of the NRF2/GPX4 antioxidant pathway. Therefore, this research underscores myricetin as a novel inducer of ferroptosis in GC cells through its interaction with NOX4. It is a promising candidate for GC treatment.

A Novel Signature Based on m6A Regulator-Mediated Genes Along Glycolytic Pathway Predicts Prognosis and Immunotherapy Responses of Gastric Cancer Patients.

N6-methyladenosine (m6A) modification is involved in many aspects of gastric cancer (GC). Moreover, m6A and glycolysis-related genes (GRGs) play important roles in immunotherapeutic and prognostic implication of GC. However, GRGs involved in m6A regulation have never been analyzed comprehensively in GC. Herein, the study aims to identify and validate a novel signature based on m6A-related GRGs in GC patients. Therefore, a m6A-related GRGs signature is established, which can predict the survival of patients with GC and remain an independent prognostic factor in multivariate analyses. Clinical significance of the model is well validated in internal cohort and independent validation cohort. In addition, the expression levels of risk model-related GRGs in clinical samples are validated. Consistent with the database results, all model genes are up-regulated in expression except DCN. After regrouping the patients based on this risk model, the study can effectively distinguish between them in respect to immune-cell infiltration microenvironment and immunotherapeutic response. Additionally, candidate drugs targeting risk model-related GRGs are confirmed. Finally, a nomogram combining risk scores and clinical parameters is created, and calibration plots show that the nomogram can accurately predict survival. This risk model can serve as a reliable assessment tool for predicting prognosis and immunotherapeutic responses in GC patients.

In situ biosynthesized polyphosphate nanoparticles/reduced graphene oxide composite electrode for highly sensitive detection of heavy metal ions.

The development of an effective sensing platform is critical for the electrochemical detection of heavy metal ions (HMIs) in water. In this study, we fabricated a newly designed sensor through the in situ assembly of reduced graphene oxide (rGO) and polyphosphate nanoparticles (polyP NPs) on a carbon cloth electrode via microorganism-mediated green biochemical processes. The characterization results revealed that the rGO produced via microbial reduction had a three-dimensional porous structure, serving as an exceptional scaffold for hosting polyP NPs, and the polyP NPs were evenly distributed on the rGO network. In terms of detecting HMIs, the numerous functional groups of polyP NPs play a major role in the coordination with the cations. This electrochemical sensor, based on polyP NPs/rGO, enabled the individual and simultaneous determination of lead ion (Pb2+) and copper ion (Cu2+) with detection limits of 1.6 nM and 0.9 nM, respectively. Additionally, the electrode exhibited outstanding selectivity for the target analytes in the presence of multiple interfering metal ions. The fabricated sensor was successfully used to determine Pb2+/Cu2+ in water samples with satisfactory recovery rates ranging from 92.16% to 104.89%. This study establishes a facile, cost-effective, and environmentally friendly microbial approach for the synthesis of electrode materials and the detection of environmental pollutants.

The emerging roles of N6-methyladenosine RNA modifications in thyroid cancer.

Thyroid cancer (TC) is the most predominant malignancy of the endocrine system, with steadily growing occurrence and morbidity worldwide. Although diagnostic and therapeutic methods have been rapidly developed in recent years, the underlying molecular mechanisms in the pathogenesis of TC remain enigmatic. The N6-methyladenosine(m6A) RNA modification is designed to impact RNA metabolism and further gene regulation. This process is intricately regulated by a variety of regulators, such as methylases and demethylases. Aberrant m6A regulators expression is related to the occurrence and development of TC and play an important role in drug resistance. This review comprehensively analyzes the effect of m6A methylation on TC progression and the potential clinical value of m6A regulators as prognostic markers and therapeutic targets in this disease.

Effect of Cold Rolling Reduction Rate on the Microstructure and Properties of Q&P Steel with a Ferrite-Pearlite Initial Structure.

Quenching and partitioning (Q&P) steel has garnered attention as a promising third-generation automotive steel. While the conventional production (CP) method for Q&P steel involves a significant cumulative cold rolling reduction rate (CRRR) of 60-70%, the thin slab casting and rolling (TSCR) process has emerged as a potential alternative to reduce or eliminate the need for cold rolling, characterized with a streamline production chain, high-energy efficiency, mitigated CO2 emission and economical cost. However, the effect of the CRRR on the microstructure and properties of Q&P steel with an initial ferrite-pearlite microstructure has been overlooked, preventing the extensive application of TSCR in producing Q&P steel. In this work, investigations involving different degrees of CRRRs reveal a direct relationship between increased reduction and decreased yield strength and plasticity. Notably, changes in the microstructure were observed, including reduced size and proportion of martensite blocks, increased ferrite proportion and decreased retained austenite content. The decrease in yield strength was primarily attributed to the increased proportion of the softer ferrite phase, while the reduction in plasticity was primarily linked to the decrease in retained austenite content. This study provides valuable insights for optimizing the TSCR process of Q&P steel, facilitating its wider adoption in the automotive sector.

Tespa1 deficiency reduces the antitumour immune response by decreasing CD8+T cell activity in a mouse Lewis lung cancer model.

Thymocyte-expressed, positive selection-associated 1 (Tespa1) is a key molecule in T-cell development and has been linked to immune diseases. However, its role in antitumour CD8+T cell immunity remains unclear. Here, we demonstrated that Tespa1 plays an important role in antitumour CD8+T cell immunity. First, compared with wild-type (WT) mice, Lewis lung cancer cells grew faster in Tespa1 knockout (Tespa1-/-) mice, with reduced apoptosis, and decreased CD8+T cells in peripheral blood and tumor tissues. Second, the proportion of CD8+T and Th1 cells in the splenocytes of Tespa1-/- mice was lower than that in WT mice. Third, Tespa1-/- CD8+ tumor-infiltrating lymphocytes (TILs) showed weakened proliferation, invasion, cytotoxicity, and protein expression of IL-2 signalling pathway components compared to WT CD8+TILs. Furthermore, PD-1 expression in CD8+TILs was higher in Tespa1-/- than in WT mice. Lastly, CD8+TILs in WT mice improved the antitumour ability of Tespa1-/- mice. In conclusion, these findings suggest that Tespa1 plays a critical role in the tumor immune system by regulating CD8+T cells.

Micrometer-precision absolute distance measurement with a repetition-rate-locked soliton microcomb.

The soliton microcomb has sparked interest in high-precision distance measurement, owing to its ultrahigh repetition rate and chip-integrated scale. We report absolute distance measurements based on synthetic wavelength interferometry with a soliton microcomb. We stabilized the repetition rate of 48.98 GHz through injection locking, with fluctuations below 0.25 Hz. Distance measurements up to 64 mm were demonstrated, presenting residuals below 2.7 µm compared with a referenced laser interferometer. Long-term distance measurements were made at two fixed positions of approximately 0.2 m and 1.4 m, resulting in a minimum Allan deviation as low as 56.2 nm at an average time of 0.05 s. The dynamic demonstration illustrated that the proposed system could track round-trip motion of 3 mm at speeds up to 100 mm/s. The proposed distance measurement system is, to our knowledge, the first microcomb-based synthetic wavelength interferometer and achieves a ranging precision of tens of nanometers, with potential applications in the fields of satellite formation flying, high-end manufacturing, and micro-nano processing.

Hierarchical porous loofah-like carbon with sulfhydryl functionality for electrochemical detection of trace mercury in water.

Mercury is a common contaminant found in natural waters, which is highly toxic to human health. Thus, the facile and reliable monitoring of mercury in waters is of great significance. In this study, we fabricated a novel loofah-like hierarchical porous carbon with sulfhydryl functionality (S-LHC), and applied it as an ultrasensitive sensor for the electrochemical detection of mercury in water. The S-LHC was prepared through the direct pyrolysis of a triazole-rich metal-organic framework (MOF), followed by chemical modification using thioglycolic acid. The highly conductive N-doped carbon framework of S-LHC facilitated the electron transfer in mercury electrochemical sensing. Meanwhile, the open hierarchical pore structure and abundant sulfhydryl groups allowed the fast diffusion and effective enrichment of mercury ions. Consequently, the S-LHC sensor exhibited an exceptionally high sensitivity for mercury ions, with the mercury detection limit (0.36 nM) orders of magnitude lower than the regulated values in drinking water (typically 10∼30 nM). The constructed sensor also afforded good anti-interference ability and excellent stability for long-term detection of mercury in a variety of complex real water samples. The present study provides not only a facile method for mercury detection, but also a new idea for the construction of highly sensitive electrochemical sensors.

Exosomal miR-let-7c-5p is involved in the cognitive function of type 2 diabetes mellitus patients by interleukin 10: A cross-sectional study.

BACKGROUND: Interleukin (IL)-10 plays a notable role in the inflammatory-associated mild cognitive impairment (MCI). We aimed to investigate whether IL-10 and its upstream factors exert an impact on MCI in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 117 T2DM patients were recruited and divided into Control group and MCI group based on the presence or absence of MCI. Clinical parameters were collected. The Montreal Cognitive Assessment (MoCA) was conducted for global cognitive function. Digit Span Test (DST), Verbal Fluency Test (VFT), and Trail Making Test-B (TMTB) were used to evaluate the executive functions of the diabetic patients. Trail Making Test-A (TMTA) was performed to examine the information processing speed function. Patients' scene memory was examined by Logical Memory Test (LMT). After the baseline data were compared, correlation and regression analyses were performed to explore the relationship among IL-10, miR-let-7c-5p and cognitive function. RESULTS: Compared to 80 patients in the control group, 37 patients in the MCI group exhibited lower IL-10 in plasma and higher miR-let-7c-5p levels in exosomes from plasma. The IL-10 level was negatively associated with MoCA. Likewise, miR-let-7c-5p levels were negatively correlated with IL-10 levels and MoCA. Elevated miR-let-7c-5p levels and decreased IL-10 levels are risk factors for MCI in T2DM patients. Increased miR-let-7c-5p and downregulated IL-10 may influence VFT and TMTB, respectively, associated with executive function. CONCLUSIONS: We demonstrated that IL-10 is correlated to the executive function of T2DM patients. Decreased IL-10 may result from the regulation of miR-let-7c-5p in exosomes.

A erythrocyte-platelet hybrid membrane coated biomimetic nanosystem based on ginsenosides and PFH combined with ultrasound for targeted delivery in thrombus therapy.

Thrombus is one of the culprits for global health problems. However, most current antithrombotic drugs are limited by restricted targeting ability and a high risk of systemic bleeding. A hybrid cell membrane-coated biomimetic nanosystem (PM/RM@PLGA@P/R) was constructed in this paper to fulfil the targeted delivery of ginsenoside (Rg1) and perfluorohexane (PFH). Poly lactic-co-glycolic acid (PLGA) is used as carriers to coat Rg1 and PFH. Thanks to the camouflage of erythrocyte membrane (RM) and platelet membrane (PM), the nanosystem in question possesses remarkable features including immune escape and self-targeting. Therefore, a compact nano-core with PLGA@P/R was formed, with a hybrid membrane covering the surface of the core, forming a "core-shell" structure. With its "core-shell" structure, this nanoparticle fancifully combines the advantages of both PFH (the low-intensity focused ultrasound (LIFU)-responsive phase-change thrombolysis) and Rg1(the antioxidant, anti-inflammatory and anticoagulant abilities). Meanwhile, PM/RM@PLGA@P/R nanoparticles exhibits superior in-vitro performance in terms of ROS scavenging, anticoagulant activity and immune escape compared with those without cell membranes (PLGA@P/R). Furthermore, in the animal experiment in which the tail vein thrombosis model was established by injecting k-carrageenan, the combined treatment of LIFU and PM/RM@PLGA@P/R showed a satisfactory antithrombotic efficiency (88.20 %) and a relatively higher biological safety level. This strategy provides new insights into the development of more effective and safer targeted biomimetic nanomedicines for antithrombotic treatments, possessing potential application in synergistic therapy field.

Consumption in Non-Pastoral Regions Drove Three-Quarters of Forage-Livestock Conflicts in China.

Forage-livestock conflict (FLC) is a major anthropogenic cause of rangeland degradation. It poses tremendous threats to the environment owing to its adverse impacts on carbon sequestration, water supply and regulation, and biodiversity conservation. Existing policy interventions focus on the in situ FLCs induced by local production activities but overlook the role of consumption activities in driving FLCs. Here, we investigate the spatiotemporal variations in China's FLCs and the domestic final consumers at the county level by combining remote sensing data and multi-regional input-output model. Results show that during 2005-2015, China's pastoralism induced an average of 82 million tons of FLCs per year. Domestic final demand was responsible for 85-93% of the FLCs in China. There was spatiotemporal heterogeneity in domestic consumption driving China's FLCs. In particular, the final demand of non-pastoral regions was responsible for around three-quarters (74-79%) of the total FLCs throughout the decade. The rangeland-based livestock raising, agricultural and sideline product processing, and catering sectors are important demand-side drivers. These findings can support targeted demand-side strategies and interregional cooperation to reduce China's FLCs, thus mitigating rangeland degradation.

Exploring choices of early nutritional support for patients with sepsis based on changes in intestinal microecology.

BACKGROUND: Sepsis exacerbates intestinal microecological disorders leading to poor prognosis. Proper modalities of nutritional support can improve nutrition, immunity, and intestinal microecology. AIM: To identify the optimal modality of early nutritional support for patients with sepsis from the perspective of intestinal microecology. METHODS: Thirty patients with sepsis admitted to the intensive care unit of the General Hospital of Ningxia Medical University, China, between 2019 and 2021 with indications for nutritional support, were randomly assigned to one of three different modalities of nutritional support for a total of 5 d: Total enteral nutrition (TEN group), total parenteral nutrition (TPN group), and supplemental parenteral nutrition (SPN group). Blood and stool specimens were collected before and after nutritional support, and changes in gut microbiota, short-chain fatty acids (SCFAs), and immune and nutritional indicators were detected and compared among the three groups. RESULTS: In comparison with before nutritional support, the three groups after nutritional support presented: (1) Differences in the gut bacteria (Enterococcus increased in the TEN group, Campylobacter decreased in the TPN group, and Dialister decreased in the SPN group; all P < 0.05); (2) different trends in SCFAs (the TEN group showed improvement except for Caproic acid, the TPN group showed improvement only for acetic and propionic acid, and the SPN group showed a decreasing trend); (3) significant improvement of the nutritional and immunological indicators in the TEN and SPN groups, while only immunoglobulin G improved in the TPN group (all P < 0.05); and (4) a significant correlation was found between the gut bacteria, SCFAs, and nutritional and immunological indicators (all P < 0.05). CONCLUSION: TEN is recommended as the preferred mode of early nutritional support in sepsis based on clinical nutritional and immunological indicators, as well as changes in intestinal microecology.

Amino-Functionalized Hierarchical Porous Carbon Derived from Zeolitic Imidazolate Frameworks for Ultrasensitive Electrochemical Sensing of Heavy Metals in Water.

Electrochemical sensing provides a feasible avenue to monitor heavy metal ions (HMIs) in water, whereas the construction of highly sensitive and selective sensors remains challenging. Herein, we fabricated a novel amino-functionalized hierarchical porous carbon by the template-engaged method using ZIF-8 as the precursor and polystyrene sphere as the template, followed by carbonization and controllable chemical grafting of amino groups for efficient electrochemical detection of HMIs in water. The amino-functionalized hierarchical porous carbon features an ultrathin carbon framework with a high graphitization degree, excellent conductivity, unique macro-, meso-, and microporous architecture, and rich amino groups. As a result, the sensor exhibits prominent electrochemical performance with significantly low limits of detection for individual HMIs (i.e., 0.93 nM for Pb2+, 2.9 nM for Cu2+, and 1.2 nM for Hg2+) and simultaneous detection of HMIs (i.e., 0.62 nM for Pb2+, 1.8 nM for Cu2+, and 0.85 nM for Hg2+), which are superior to most reported sensors in the literature. Moreover, the sensor displays excellent anti-interference ability, repeatability, and stability for HMI detection in actual water samples.